The objectives of this research are to define in the human fetus, amniotic fluid, fetal membranes, and uterine decidua the events that constitute a metabolic communication system, and to identify those fetal maturational events which initiate human parturition. We propose that the initiation of parturition is a consequence of fetal brain maturation, pituitary-fetal adrenal secretory processes and altered progesterone metabolism in fetal membranes; that lysosomal phospholipase A2, in fetal membranes and uterine decidua catalyzes release of arachidonic acid from glycerophospholipids in these tissues; and that free arachidonic acid is converted by the prostaglandin synthetase complex to prostaglandins and related compounds which facilitate myometrial contraction. We propose to investigate the ontogenesis of the human hypothalamic-pituitary vasculature, the ontogenesis of the subcellular compartmentalization of hypothalamic hormones, and the control of secretion of pituitary hormones; to identify the factors controlling growth and steroidogenesis of the fetal adrenal; to elucidate steroid hormone synthesis and metabolism in the placenta, fetal membranes, and uterine decidua; to characterize the subcellular localization of phospholipase A2 in fetal membranes and uterine decidua; to eluciate the biogenesis and regulation of prostaglandin and prostaglandin-related substances in the initiation of labor; to characterize the distribution of progesterone in fetal membranes throughout gestation; and to determine the role of fetal progesterone binding protein in the intracellular distribution of progesterone and in the metabolism of lysosomes. We will assess the epidemiologic factors of prematurity and develop a regional perinatal program for identification of gravidas at risk of prematurity. We will evaluate the impact of uteroplacental perfusion of therapeutic regimens used in preventing or arresting premature labor, and attempt to define the metabolic aberrations that cause premature labor.